Mosquito-borne parasites and viruses continue to inflict severe morbidity and mortality on human populations across the plobe. Advances in molecular genetic studies of mosquitoes have raised hopes for the development of novel methods of disease control or prevention. There are now several examples whereby the introduction of exogenous molecules into mosquitoes has resulted in a transmission-blocking effect for a particular virus or parasite. The recent development of genetic transformation systems for the mosquito, Aedes aegypti, will allow the expression of these molecules within the mosquito in a heritable, rather than transient manner. The ability to specifically interfere with pathogen development and transmission during the course of a vector-host cycle will undoubtedly assist in the elucidation of vector-pathogen interactions. Furthermore, it has been postulated that a transmission-blocking strain of mosquitoes could be used to replace a wild type, pathogen-transmitting strain of mosquitoes. This would require a mechanism to drive the refractory gene into the population in an active manner, rather than relying on the release of large numbers of individuals and Mendelian inheritance to spread the gene of interest. Among the proposed methods of driving refractory genes into wild populations, is the use of transposable element mobility to overcome the limitations of Mendelian inheritance. This proposal is designed to test the ability of the mariner element from Drosophila mauritiana, Mos1, to mobilize in the Ae. Aegypti genome and spread through a cage population of mosquitoes. The specific aims are as follows. 1) Determine where in the Mos1 element a marker gene can be inserted without disrupting autonomous transpositional activity and test the active Mos1 constructs for transpositional activity in Ae aegypti. 2) Characterize Mos1 insertion events in Ae aegypti by localizing the event to chromosome(s) and determining the impact of the event on normal gene expression. 3) Generate transgenic lines of Ae. Aegypti that contain a marked, autonomous Mos1 element. 4) Assess the ability of the active Mos1 elements to mobilize in the Ae. Aegypti genome and spread through a cage population.